Topical Ceramide Corrected Epidermal Cell Hyperproliferation and Stratum Corneum Dysmaturation in Atopic eczema

Umeda, Yumi; Mizutani, Hitoshi; Imokawa, Genji; Shimizu,

doi:10.1007/978-3-642-60419-5_38

Cited by 13 publications

(11 citation statements)

References 6 publications

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“…In AD skin, we have consistently found that the acylceramide deficiency exists to the highest degree among several ceramide species, being predominantly attributable to the barrier disruption constitutively seen even in the non-lesional skin of patients with AD [6]. The essential contribution of acylceramide to the disrupted barrier function in AD skin was also corroborated by the evidence that topical application of pseudo-acylceramide containing ester-linked linoleic acid to the skin of patients with AD completely restored the skin barrier disruption and recovered of TEWL values to healthy control levels [34]. Since this barrier-disrupted situation in the clinically normal skin of patients with AD may be responsible for the etiological background of AD, and since the observed deficiency of acylceramide is highly dependent upon the barrier disruption found in AD skin, it is of considerable importance to determine the biochemical mechanism(s) involved in the down-regulation of acylceramide production in order to elucidate the pathogenesis of AD and its predisposition toward recurrent dermatitis.…”

Section: Gcer Deacylase Activity In Admentioning

confidence: 64%

A possible mechanism underlying the ceramide deficiency in atopic dermatitis: Expression of a deacylase enzyme that cleaves the N-acyl linkage of sphingomyelin and glucosylceramide

Imokawa

2009

Journal of Dermatological Science

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Section: Gcer Deacylase Activity In Admentioning

confidence: 64%

A possible mechanism underlying the ceramide deficiency in atopic dermatitis: Expression of a deacylase enzyme that cleaves the N-acyl linkage of sphingomyelin and glucosylceramide

Imokawa

2009

Journal of Dermatological Science

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“…The essential contribution of acylceramide to the disrupted barrier function in skin with AD was also corroborated by the evidence that the topical application of pseudoacylceramide-containing ester-linked linoleic acid to the skin of patients with AD completely restored the skin barrier disruption with clinical improvement as revealed by the recovery of transepidermal water loss values to healthy control levels (Umeda et al, 1997). Because this barrier-disrupted situation in the clinically normal skin of patients with AD may be responsible for the etiological background of AD and because the observed deficiency of acylceramide is highly dependent on the barrier disruption found in skin with AD, it is of considerable importance to determine the biochemical mechanism(s) involved in the down-regulation of acylceramide production to elucidate the pathogenesis of AD and its predisposition toward recurrent dermatitis.…”

Section: Discussionmentioning

confidence: 75%

Abnormal Expression of the Novel Epidermal Enzyme, Glucosylceramide Deacylase, and the Accumulation of its Enzymatic Reaction Product, Glucosylsphingosine, in the Skin of Patients with Atopic Dermatitis

Ishibashi

Arikawa

Okamoto

et al. 2003

Laboratory Investigation

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SUMMARY:To clarify mechanisms underlying acylceramide deficiency as an causative factor of the permeability barrier disruption seen in the skin of patients with atopic dermatitis (AD), we hypothesized and then demonstrated the presence of a novel epidermal enzyme, termed glucosylceramide (GC) deacylase. This enzyme hydrolyzes (acyl)GC at the N-acyl site to yield its lysoform, glucosylsphingosine (GS), instead of the formation of (acyl)ceramides by ␤-glucocerebrosidase. Assays of enzymatic activity using [palmitic acid-14 C] GC as a substrate revealed that extracts from the stratum corneum and from the epidermis (but not from the dermis) of patients with AD have the significantly higher potential to hydrolyze GC at the N-acyl site to release 14 C-labeled free fatty acid than of healthy controls. To determine the in vivo physiologic function of this novel enzyme, we measured the metabolic product GS in the upper stratum corneum. In both the involved and the uninvolved stratum corneum from patients with AD, there were significant increases in the amounts of GS compared with healthy controls and there was a significant inverse correlation with the decreased content of ceramides or ceramide-1 (acylceramide). Thus, collectively these results strongly suggest the physiologic relevance of GC deacylase to the acylceramide deficiency seen in the stratum corneum of patients with AD. (Lab Invest 2003, 83:397-408).A deficiency of ceramides in the stratum corneum is an causative factor of the barrier-disrupted and dry skin of patients with atopic dermatitis (AD) (Imokawa et al, 1991). This dysfunction of the stratum corneum leads to a high vulnerability to irritants or allergens, which results in the induction, recurrence, or refractory nature of the dermatitis. Thus, it is intriguing to determine the biochemical mechanism(s) underlying the ceramide deficiency because it may be linked to the physiopathogenesis of AD. In the epidermis of patients with AD, we have previously demonstrated the accentuated expression of a hitherto undiscovered epidermal enzyme, termed sphingomyelin (SM) deacylase, which was associated with the reduced ceramide mass in the stratum corneum as a result of its competition with the ceramideproducing enzyme sphingomyelinase (SMase) for the common substrate SM Murata et al, 1996). Recently, it was reported that omega-OH ceramide, an important acylceramide precursor, does not derive from SM in the mammalian stratum corneum, which suggests that it derives solely from glucosylceramide (GC) precursors (Uchida et al, 2000). Thus, it is likely that acylceramides are biosynthesized not by the hydrolysis of SM but through pathways involving the deglucosylation of acylglucosylceramides by ␤-glucocerebrosidase (GlCdase). On the basis of these findings, the acylceramide deficiency observed in AD could not be explained in terms of the up-regulation of SM deacylase. As a resolution for this discrepancy, we hypothesized the existence of a novel epidermal enzyme, termed here GC deacylase, which hydrolyzes (acyl)GC at t...

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“…In relation to the pathogenic mechanism leading to the barrier perturbation, we demonstrated that there is a signifi cant decrease in ceramide content even in the uninvolved stratum corneum of AD skin compared with healthy control skin [3,29] , indicating that ceramide defi ciency is an etiologic factor for the barrier-disrupted and dry skin of patients with AD. Since it is well established that natural or synthetic ceramide is effective in replenishing the barrier function when topically applied to experimentally barrier-disrupted skin [1,2,30] , it seems reasonable to assume that topical application of ceramides is better suited for attenuating the barrier disruption in the nonlesional skin which has signifi cantly downregulated ceramide production. Further, as the level of barrier disturbance seen in the nonlesional skin of AD patients increases in proportion to the severity of the disease [25] , characterizing the effect of ceramide treatment in terms of repairing the barrier function would provide insight into the importance of the disrupted barrier function as an etiologic factor in the pathogenesis of AD.…”

Section: Discussionmentioning

confidence: 99%

Reevaluation of the Importance of Barrier Dysfunction in the Nonlesional Dry Skin of Atopic Dermatitis Patients through the Use of Two Barrier Creams

Matsuki¹,

Kiyokane²,

Matsuki³

et al. 2004

Exog Dermatol

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Background: Atopic dermatitis (AD) can be considered a barrier disease in which antigens and irritants that can easily penetrate clinically normal, nonlesional skin due to its defective barrier function trigger and worsen the dermatitis. Thus, replenishing the barrier function in clinically normal, nonlesional skin of patients with AD seems to be a key for preventing the refractory nature of the dermatitis. Objective: To determine whether the disrupted barrier function of AD nonlesional skin can be repaired by topical application of a synthetic ceramide known to induce barrier recovery and to subsequently evaluate the relationship between enhanced barrier function and improved dry skin conditions. Methods: We applied topically a synthetic ceramide (CER) or hirudoid (HIRU)-containing cream to the nonlesional skin of AD patients for 4 weeks and evaluated their efficacy by measuring transepidermal water loss (TEWL) and capacitance values as well as clinical scoring for scaling/dryness/itchiness. Results: Treatment for 4 weeks with the CER cream significantly reduced dryness/scaling/itchiness which was accompanied by significant decreases in TEWL and increases in capacitance values at 2 and 4 weeks. In contrast, treatment for 4 weeks with the HIRU cream elicited a similar but lesser reduction in dryness/scaling/itchiness which was accompanied by significant but lesser decreases and increases in TEWL and capacitance values, respectively, at 2 and 4 weeks. Comparison of TEWL and capacitance values during the 4 weeks of treatment with CER or HIRU creams revealed that while the two parameters of CER cream-treated skin were generally similar to healthy control skin, those of the HIRU cream-treated skin remained similar to mild or moderate AD skin. Conclusion: It is likely that the recovery of barrier function reflects the improvement in clinically evaluated dry skin conditions of the nonlesional skin to a greater extent than that in water deficiency, which suggests that the barrier-replenishing effect is a more important factor for treatment of AD nonlesional skin than is the improvement of water deficiency.

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Topical Ceramide Corrected Epidermal Cell Hyperproliferation and Stratum Corneum Dysmaturation in Atopic eczema

Cited by 13 publications

References 6 publications

A possible mechanism underlying the ceramide deficiency in atopic dermatitis: Expression of a deacylase enzyme that cleaves the N-acyl linkage of sphingomyelin and glucosylceramide

A possible mechanism underlying the ceramide deficiency in atopic dermatitis: Expression of a deacylase enzyme that cleaves the N-acyl linkage of sphingomyelin and glucosylceramide

Abnormal Expression of the Novel Epidermal Enzyme, Glucosylceramide Deacylase, and the Accumulation of its Enzymatic Reaction Product, Glucosylsphingosine, in the Skin of Patients with Atopic Dermatitis

Reevaluation of the Importance of Barrier Dysfunction in the Nonlesional Dry Skin of Atopic Dermatitis Patients through the Use of Two Barrier Creams

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